Brain arteriovenous malformations (AVMs) have been the subject of a 15-year study at our institution. Our first efforts were to identify factors predictive of post-operative perfusion- breakthrough hemorrhage, then of cerebral 'steal', and more recently of risk factors predicting first and recurrent hemorrhage, single-center treatment study including quantitation of 'eloquence', and most recently a population-based prospective collection of AVM incidence hemorrhage and estimates of outcome and efforts to developed a world-wide study of this complex low- frequency illness. The current proposal is, in part, a continuation of work funded by prior RO1s, mainly NS-34747 relocated as of 1-Jan-2000 to Univ Calif San Francisco by the our long-term collaborator PI, WL Young, now a newly-chaired Professor of Research Anesthesia there, but also a change in focus and extension into new areas which we believe justifies our application for new funding. Dr Young's plans for an AVM project in San Francisco should lead to the development of another project which we hope can eventually lead to a bi-coastal effort. Three proposals are made. Specific aim 1 is a population-based acquisition of the incidence of AVM hemorrhage, its morbidity, and mortality drawn from the roughly 9,000,000 population in the `New York Islands' (Manhattan, Staten Island, and Long Island - including Queens, Brooklyn, and Nassau and Suffolk Counties), a study begun within the last year. The feasibility has been tested, the goals expanded, and data collection is well under way. The results are expected to provide useful assessments for AVM hemorrhage to permit better decisions for treatment versus conservative follow-up, and allow estimates of comparative costs of each of the current management plans. Specific aim 2 is to bring to fruition our worldwide web site for AVMs. The initial steps taken with colleagues from 19 countries to date has revealed the need for consensus on the interpretation of AVM imaging, planned for its first meeting in Feb-2000. Following consensus, centers whose population-based capabilities (i.e., Singapore, a population of 4,000,000 served by three hospitals some of whose staff members trained with us) will provide a means to test the risk factors for hemorrhage created from our referral-based Columbia center and identify possible other factors not represented in our data base. The findings will also test our current center-based data for the morphologic imaging characteristics of AVM in predicting hemorrhage. The two preceding aims should permit estimates for the formulation of a clinical trial, but we cannot promise the organization of a trial until more complete data available. Specific aim 3 is our proposal for a single-center treatment study, including more intensive studies of 'eloquence', a term in current use to decide suitability for treatment, but one based on largely-outmoded concepts of anatomical-clinical correlations. The methods employed are on-the-table assessments of cerebral function derived from Behavior Science principles and undertaken with local anesthesia challenges using agents with differential effects on brain white and gray matter. The results are improving the prediction for short- and long-term outcome for embolization and surgery.